On Dec. 30, 1998, the assignee hereof filed a U.S. nonprovisional patent application for an applicant hereof, Dr. Craig Grimes, currently pending as Ser. No. 09/223,689 entitled xe2x80x9cRemote Magneto-elastic Analyte, Viscosity and Temperature Sensing Apparatus and Associated Methods of Sensingxe2x80x9d. On Feb. 11, 2000 the assignee hereof filed a U.S. nonprovisional patent application for applicants hereof, Dr. Craig Grimes and Dr. Dimitris Kouzoudis, currently pending as Ser. No. 09/502,663 entitled xe2x80x9cMagnetoelastic Sensing Apparatus and Method for Remote Pressure Query of an Environment.xe2x80x9d
In general, the present invention relates to telemetry techniques for direct measurement of, as well as measuring changes in, material characteristics such as mass, thickness, density, and elasticity. More particularly, the invention is directed to a new apparatus and method for remotely measuring or monitoring changes in characteristics relating to the elastic nature of a material at least partially coating a surface of a magnetostrictive element, including determining a modulus of the material""s elasticity or viscous nature (e.g., Young""s modulus), bulk modulus, or other such constant or coefficient expressing the degree to which a substance or material is elastic or viscous in nature), monitoring or measuring bioactive reaction responses of the material, such as coagulation reactions, blood clotting time, and so on. The sensor element is preferably remotely located (no hardwire interconnection) from an associated pick-up/receiver(s) and data processing unit(s). The thin-film/coating layer in contact with a surface of a base element may be any of a variety of inert thin-film layers or chemically-, physically-, or biologically-responsive layers (such as blood, which experiences a change in viscosity as it coagulates) for which data or material property information about the layer is desired. Among the many suitable thin-film layers for the sensor element of the invention are fluent bio-substances (such as those comprising a biologic agent or blood), thin-film deposits used in a manufacturing process, a polymeric coating, a coating of paint, and a coating of an adhesive, etc.
In one aspect of the invention, the focus is on an apparatus and technique for direct quantitative measurement of elasticity characteristic values of an unknown thin-film/coating layer (which relate to a change in mass of a bare magetoelastic element and one with any unknown coating/film in contact with a surface of the base magnetoelastic element). In another aspect of the invention, the focus is on an apparatus and technique for determining elasticity characteristics where the thin-film layer is a fluent bio-substance. In such cases, as one can appreciate, of interest in connection with a fluent substance-prior to setting, curing or drying-is its viscous nature or behavior. Fluent substances that have transformed into a solid state, are said to have xe2x80x98setxe2x80x99, xe2x80x98curedxe2x80x99, or xe2x80x98driedxe2x80x99 (e.g., coagulated blood). The bio-substance can comprise a bio-component such as a biologic agent or blood, a non-Newtonian liquid (often making direct quantitative measurement of its characteristics using standard models and testing procedures, inaccurate). Biologic agents of interest include an antibody, a biochemical catalyst (or biocatalyst) such as an enzyme, a disease-producing agent (or pathogen) a DNA component, and so on.
Although magnetoelastic materials are currently used in connection with position sensors, identification markers, and in the commercial retail arena as anti-theft or, electronic article surveillance (EAS) tags, according to the unique technique of the invention, by examining the shift in the resonant frequency of a magnetoelastic sensor element of the invention to which a given mass load (coating/film/layer) has been applied, the elastic modulus Y if the mass load can be determined where density p of the coating/film/layer is known. One important aspect of the invention relates more-particularly to techniques for measuring the viscoelastic properties of blood, including blood coagulability tests and other techniques that measure bioactive coagulation reactions. This aspect of the invention relates specifically to a new remote-query technique for measuring coagulation/clotting time of blood, or other such bioactive coagulation reaction, whereby a drop/coating of the responsive-material (e.g., blood) is placed in contact with a surface of the magnetoelastic sensor element/substrate to which a magnetic field (having an alternating magnetic field component and a DC magnetic biasing field component) is then applied.
Anti-theft markers/tags (electronic article surveillance, EAS, markers) generally operate by xe2x80x9clisteningxe2x80x9dfor acoustic energy emitted in response to an interrogating AC magnetic field, to sense the presence of an EAS marker. Sensormatic, Inc. distributes an EAS tag (dimensions 3.8 cm xc3x971.25 cm xc3x970.04 mm) designed to operate at a fixed frequency of 58 kHz (well beyond the audible range of human hearing). These EAS tags are embedded/incorporated into articles for retail sale. Upon exiting a store, a customer walks through a pair of field coils emitting a 58 kHz magnetic field. If a tag is still in an article being carried by the customer, the tag will likewise emit a 58 kHz electromagnetic signal that can be detected using a pickup coil, which in turn may set off an audible or visual alarm. More-recently, these tags are being placed in a box-resonator, sized slightly larger than the tag, such as the tags placed within a cavity 20 of a housing (see FIG. 2 of Winkler et al., U.S. Pat. No. 5,499,015-or simply ""015).
Winkler et al. (""015) describes an electronic article surveillance (EAS) anti-theft system that operates by detecting mechanical resonances of magnetostrictive elements made of amorphous metallic glass METGLAS(copyright)2826 MB, to prevent or deter theft of merchandise from retail establishments. In response to an interrogation signal generated by energizing circuit 201, the interrogating coil 206 generates an interrogating magnetic field, which in turn excites the integrated marker portion 12 of the article of merchandise 10 into mechanical resonance. During the period that the circuit 202 is activated, and if an active marker is present in the interrogating magnetic field, such marker will generate in the receiver coil 207 a signal at the frequency of mechanical resonance of the marker. This signal is sensed by a receiver which responds to the sensed signal by generating a signal to an indicator to generate an alarm.
Anderson, III et al., U.S. Pat. No. 4,510,489-or simply ""489 discloses a marker 16 (HG. 5) formed of a strip 18 of a magnetostrictive, ferromagnetic material adapted, when armed in its activated mode, to resonate mechanically at a frequency within the range of the incident magnetic field. A hard ferromagnetic element 44 disposed adjacent to the strip 18 is adapted, upon being magnetized, to magnetically bias the strip 18 and thereby arm it to resonate at that frequency. An oscillator provides an AC magnetic field within interrogation zone 12 to mechanically resonate a magnetostrictive strip 18, which has first been armed by a magnetized hard ferromagnetic element 44, upon exposure to this AC magnetic field. The sole object of Anderson, III et al. (""489) EAS marker is to detect the presence between coil units 22 and 24 (interrogation zone 12) of an xe2x80x9carmed/activatedxe2x80x9d marker 16. In the event an activated marker 16 secured to a retail article is detected within zone 12, an alarm will sound. A deactivator system 38, electrically connected to a cash register, can be used to deactivate the marker.
Humphrey, U.S. Pat. No. 4,660,025 and, another reference, Humphrey et al., U.S. Pat. No. 4,980,670 disclose harmonic type electronic article surveillance (EAS) markers which include a thin strip or wire of magnetic material that responds to an alternating interrogation signal by generating a signal pulse that is rich in high harmonics of the interrogation signal. Schrott, et al., U.S. Pat. No. 5,552,778-or simply ""778 describes a multibit bimorph magnetic ID tag for attachment to, and identification of, an object. The tag has one or more bimorphs comprised of a thin strip of a magnetostrictive material attached to a thicker bar 21 of hard magnetic material. A shipping pallet, package, or product is tagged with the bimorph for later product identification. Schrott et al. (""778) indicates that a multibit tag could be programmed to generate a binary or other suitable code. In the binary code case, a certain frequency of an array of cantilevers can be assigned a value of xe2x80x9czeroxe2x80x9d or xe2x80x9conexe2x80x9d and, if absent, it can take the opposite value. The Schrott, et al. (""778) ID tag is limited to coded (zeros and ones) identification of the object. If, in operation, a Schrott, et al. (""778) ID tag""s resonant frequency (predetermined by size/materials) is not xe2x80x9chitxe2x80x9d during interrogation due to some unexpected event/external factor (such as, its resonant frequency is changed due to a temperature swing, or due to reaction of the ID tag with a surrounding fluid), no response will be detected and an incorrect output code will result, thus, destroying the Schrott, et al. (""778) ID tag""s function.
Rather than working at a fixed interrogation frequency and simply checking for amplitude like the anti-theft EAS markers do to sense presence or absence of an active EAS tag on an article for purchase, the novel sensing apparatus and method of the invention looks to the frequency response of the sensor for information about the elasticity characteristics of a thin-film layer atop a magnetoelastic base element. Operating as a telemeter, elasticity characteristics of the thin-film layer can be obtained through remote query according to the invention, without direct hard-wire connection and without the need to ensure the sensor element""s orientation in order to provide such information. In effect, the interrogation field to which the sensor element is exposed acts as a power source for the xe2x80x98passivexe2x80x99 sensing elements of the invention which, in turn, transmits or emits information magnetically, acoustically, and optically.
Knowledge of the elastic properties and characteristics of materials, including stress-strain relationships, visco-elastic behavior over time (whether or not exposed to an external agent such as air or other gas), viscous nature or behavior, brittleness, bioactive reaction response, and so on, often factors heavily into engineering product and manufacturing process design and analysis. Elastic moduli are closely linked to the internal structure of solids at their atomic and microstructural levels, thus offering valuable information for materials research and development. The American Heritage Dictionary, Second College Edition, published by Houghton Mifflin Company, Boston, 1982, a revised edition of New college ed. c1976, defines a modulus as: xe2x80x9c1. Physics. A constant or coefficient that expresses the degree to which a substance possesses some property.xe2x80x9d Measurements of the elastic moduli and their dependency on ambient conditions, for example temperature and pressure, help to evaluate material properties, material composition, and the utility for an intended application such as thin film deposition, or deposition of specific alloy composition in microcircuit device fabrication, and layering or lamination in a medical device.
In general, coagulation is the separation or precipitation from a dispersed state of suspensoid particles resulting from their growth-the separation or precipitation resulting from prolonged heating, the addition of an electrolyte, a condensation reaction between solute and solvent, and so on (an example of which is the setting of a gel). Blood, a fluent connective tissue consisting of plasma and cells, is an example of a bio-substance that coagulates. The unique nature of blood, has caused it to be characterized as a non-Newtonian fluid; thus posing a challenge for those needing to measure bioactive reactions, as well as determine clotting and coagulation time. It is important to reliably ascertain specific information about blood and other bio-components in order to perform coagulation monitoring for surgical procedures and to monitor anticoagulant therapy delivered to patients in connection with cardiac monitoring. The coagulation process of blood relies on a well known protein cascade and its interaction with blood cells and local tissue factors (see, for reference, the pages numbered 23 -25 of applicants"" provisional application No. 60/271,099 filed Feb. 23, 2001). Consequently the bleeding time at a surface wound will significantly differ from blood coagulation time in-vivo. Current methodologies for determining blood coagulation time rely on isolation of specific factors, thus requiring the removal of red blood cells to determine a plasma/fibrinogen isolated clotting time. Blood coagulability tests currently in use, clinically test the ability of blood to coagulate, such as to determine clot retraction time and quantification, prothrombin time, partial thromboplastin time, and platelet enumeration. For general reference concerning one such conventional technique, called Surface Plasmon Resonance (SPR), along with a discussion of the process of blood coagulation, please see the article entitled xe2x80x9cSurface plasmon resonance (SPR) analysis of coagulation in whole blood with application in prothrombin time assayxe2x80x9d, K. M. Hansson, et al. Biosensors and Bioelectronics 14 (1999), 671-682. The apparatus and method of the invention provides a novel testing technique that can be used to determine elasticity characteristics of blood and other fluent bio-substances-of greatest interest prior to coagulation or drying being the viscous nature or behavior thereof-as a stand-alone test or used to supplement any of the testing modalities currently available to characterize blood.
It is a primary object of the invention to provide apparatus and technique for obtaining quantitative direct measurement of, as well as measuring or monitoring changes in, characteristics relating to the elastic nature of a material layer at least partially coating a surface of a base magnetostrictive element. Elasticity characteristics of interest include a modulus of elasticity (Young""s modulus) value for the material, a bulk modulus value for the material, and monitoring or measuring bioactive reaction responses of the material, such as coagulation reactions, blood clotting time, and so on. No direct hard-wire connection to an interrogation field generating coil or to a magneto-elastic emission receiving coil, is needed; but rather the receiver unit is remotely located for the sensing.
As can be appreciated, the innovative compact apparatus and method use a base magnetostrictive element to which a thin-film layer has been added/deposited/layered as contemplated and described herein, accommodate a variety of measurement and monitoring techniques and structural alternatives, including but not limited to the following identified featuresxe2x80x94all within the spirit and scope of design goals contemplated hereby. Advantages of providing the new elasticity sensing apparatus and associated method, include without limitation:
(a) The invention can be used for one-time disposable operation (e.g., in the form of a kit) or continuous monitoring of a particular thin-film/coating/layer to observe characteristics of the thin-film as it reacts to some agent over time (e.g., observing blood as it coagulates to create a coagulation response curve or determine a blood clotting time);
(b) Versatilityxe2x80x94The invention can be used to measure physical properties of a wide range of thin-films/coatings in connection with biomedical applications (such as within medical test samples), manufacturing operations, material science research tool applications, and so on. In the context of a disposable kit or tool for monitoring a bio-substance having a component such as a biologic agent (biocatalyst, pathogen, DNA component, etc.) or blood, the apparatus provides a portable point-of-care diagnostic tool for real-time, immediate as well as ongoing monitoring of an anticoagulation, or other medicine, therapy-such as might be needed during, prior to, or post-surgery or treatment. By offering nearly-instantaneous results, one eliminates the need for long-term storage of blood and anticoagulant treatment prior to performing the characterization of the blood (esp. since storage and such treatment may cause erroneous results).
(c) Simplicity of usexe2x80x94The new sensing apparatus can produce measurement results with relative ease. Monitoring and measurement of a variety of elasticity characteristics may be performed without requiring sophisticated equipment and complicated procedures. For example, real-time monitoring of the deposit of a layer(s) in a wafer or microchip fabrication process can take place by positioning sensor elements within a vacuum chamber/clean room and remotely measuring emissions from outside the chamber, while the manufacturing process is taking place. Further, the simplicity of design allows for ready incorporation of a sensing element of the invention into self-diagnostic kits (such as is presently available for glucose monitoring of diabetic patients). The relatively small amount of blood necessary for characterization utilizing the sensing system of the invention makes collection from an unsedated, conscious patient less troublesome. Present monitoring practices require the removal of relatively large blood samples (2-10 ml) and extensive sample preparation prior to titration analysis resulting in a prolonged testing regime, which can require several hours for result generation. Use of a sensing kit incorporating a sensing element of the invention significantly reduces testing time, blood volume removed (patient distress) while still providing comparative results.
(d) Speed of resultsxe2x80x94The speed with which blood, or other sample-fluent bio-substance, may be characterized using the sensing element of the invention allows it to be used in connection with surgical procedures where constant, real-time monitoring (sampling and ready results) of blood coagulation is critical. Certain medication therapy requires, at times, nearly instantaneous evaluation/results. For example, use of anticoagulation therapy is extensive during certain cardiac surgical procedures; and whether done as an in-patient, or out-patient basis, speedy results are often imperative.
(e) Structural designxe2x80x94The thin-film layer of interest adhered to the magnetostrictive base may be shaped or applied in a manner that optimizes the speed at which an activity, reaction, or response occurs over time to an external agent (e.g., air or humidity), allowing the sensor apparatus to provide useful information at a faster rate. The sensor elements can be formed into many different shapes of various sizes; for example, the sensor elements may be fabricated on a micro-circuit scale for use where space is extremely limited such as within small-sized sealed packaging or medical test samples (e.g., a test tube), or on a larger scale.
(f) Several sensor elements may be incorporated into an array to provide a xe2x80x98packagexe2x80x99 of various information relating to elasticity characteristics of the thin-film layer by sampling simultaneously or sequentially, each of several different base elements having various different thin-film layers.
(g) Receiving unit design flexibility-One unit may be built with the capacity to receive acoustic emissions (elastic waves with a frequency up into the gigahertz, GHz, range) as well as electromagnetic emissions emanating from the sensor element, or separate acoustic wave and electromagnetic wave receiving units may be used.
(h) Apparatus design simplicityxe2x80x94Reducing the number and size of components required to accomplish measurements/monitoring of elasticity characteristics reduces overall fabrication costs, making kits economically feasible, and adds to ease of operation.
Briefly described, once again, the invention includes an apparatus for determining elasticity characteristics of a thin-film layer. By way of example only, occasional reference will be made, here, to FIG. 17 where certain core, unique features of method 100 are labeled. The apparatus comprises a sensor element having a base magnetostrictive element at least one surface of which is at least partially coated with the thin-film layer. The thin-film layer may be of a wide variety of materials (having a synthetic and/or bio-component) in a state or form capable of being deposited, whether manually or otherwise layered, on the base element surface, such as by way of eye-dropper, melting, dripping, brushing, sputtering, spraying, etching, evaporation, dip-coating, laminating, and so on. Among the many suitable thin-film layers for the sensor element of the invention are fluent bio-substances (such as those comprising a biologic agent or blood), thin-film deposits used in a manufacturing process, a polymeric coating, a coating of paint, and a coating of an adhesive, and so on.
There are many further distinguishing features of the apparatus and method of the invention. A receiver, preferably remotely located from the sensor element, is used to measure a plurality of values for magneto-elastic emission intensity of the sensor element (box 104): (a) in one characterization, the measure of the plurality of values is used to identify a magneto-elastic resonant frequency value for the sensor element (box/ 106); and (b) in another characterization, the measure of the plurality of successive values is done at a preselected magneto-elastic frequency, fx (box 107) where, for example, (the magneto-elastic resonant frequency, fo, of the sensor element may be preselected as fx, or some other selected frequency may be selected). In characterization (a), using a value for density of the thin-film layer and a value for mass of the base magnetostrictive element and the magneto-elastic resonant frequency value so identified, at least one of the elasticity characteristics for the thin-film layer can be determined (box 108). In characterization (b), an elasticity response profile for the thin-film layer (here, a bio-substance) can be produced by using the values for emission intensity measured (box 109). Elasticity characteristics that may be determined according to the invention include any modulus/value (boxes 108, 110, 112), as well as any elasticity response profile (box 109), that provides information as to the elasticity or general elastic nature of the thin-film layer material, including among other things: the modulus of elasticity, Young""s or other modulus, Yc, or bulk modulus; any bioactive reaction response curve, such as a coagulation reaction curve for the bio-substance; and in the case of blood, a blood clotting (or coagulation) time. For example, a coagulation reaction curve (or other bioactive reaction response curve) may be produced according to the invention by plotting, over a selected response-time interval, a plurality of successive voltage values respectively associated with the plurality of successive values for magneto-elastic emission intensity measured.
A value for the modulus of elasticity, Yc, of the thin-film layer can be directly obtained using an apparatus and method of the invention according to the expression:                               Y          c                =                                            ρ              c                        ·            4                    ⁢                      L            2                    ⁢                                    f              0              2                        ·                                                            ∑                                      i                    =                    1                                    N                                ⁢                                                      (                                                                                            (                                                                                    f                              i                              xe2x80x2                                                                                      f                              0                                                                                )                                                2                                            -                                                                        m                          0                                                                          m                          i                          xe2x80x2                                                                                      )                                    ⁢                                      (                                          1                      -                                                                        m                          0                                                                          m                          i                          xe2x80x2                                                                                      )                                                                                                ∑                                      i                    =                    1                                    N                                ⁢                                                      (                                          1                      -                                                                        m                          0                                                                          m                          i                          xe2x80x2                                                                                      )                                    2                                                                                        Eqn        .                  xe2x80x83                ⁢        1            
Eqn. 1 represents the general case where several thin-film layers from 1, 2, . . . N are applied consecutively (i =1,2 . . .N) to a base magnetostrictive element. As is readily apparent, Eqn. 1 is simplified where only one thin-film layer is deposited, thus, i =1 and no summation is necessary. Here, m0 is the initial mass of the base element (without a thin-film layer) and f0 is the base element""s resonant frequency measured with no thin-film layer. Once the base element is at least partially coated with one or more thin-film layers, a new mass mixe2x80x2 and resonant frequency fixe2x80x2 of the sensor element measured after each coating/layer is applied, are used in the summation of Eqn. 1. Thus, where a single layer is applied to the base element i =1 and no summation is necessary, and one can readily appreciate that Eqn. 1 simply reduces to the following expression for modulus value, Yc:       Y    c    =                    ρ        c            ·      4        ⁢          L      2        ⁢                  f        0        2            ·                        (                                                    (                                                      f                    xe2x80x2                                                        f                    0                                                  )                            2                        -                                          m                0                                            m                xe2x80x2                                              )                                      (                          1              -                                                m                  0                                                  m                  xe2x80x2                                                      )                    2                    
wherein pc denotes density of the thin-film layer, L denotes length of the base element, m0 denotes a mass of the base element (i.e., without a thin-film layer yet applied), f0 represents the resonant frequency of the magnetostrictive element measured with no thin-film layer yet applied, mxe2x80x2 denotes a mass of the sensor element (i.e., including the base element coated with thin-film layer), and fxe2x80x2 denotes a resonant frequency of the base element measured with the thin-film layer applied.
The biologic agent and other components in the thin-film layer are preferably compatible so that any reaction or activity of the thin-film layer intended for monitoring according to the invention, will take place within the time interval during which values for magneto-elastic emission intensity of the sensor element are measured. The biologic agent can include is antibody, a biochemical catalyst, or biocatalyst, such as an enzyme, a disease-producing agent, or pathogen, a DNA component, and so on, included at as a component of the thin-film layer and for which information and/or monitoring of identified elasticity characteristics is desired. The base magnetostrictive element may be made of an alloy of an element selected from many elements known to have mangetostrictive properties such as iron, cobalt, samarium, yttrium, gadolinium, terbium, and dysprosium. The base element may take on a wide variety of shapes having at least one surface on which the thin-film layer can be deposited or layered, including elongated ribbon shapes, rectangular-elongated (whereby a length, l, of the sensor element is at least twice its width, w), circular, oval, polygonal, etc.; those shapes that allow sufficient vibration of the sensor element and remote receipt of its emissions, are preferred. Depending upon the means of depositing employed, the thin-film layer can readily be applied so that its thickness, ttf, is less than a thickness, tmag, of the base magnetoelastic element (such as could be the case if the thin-film layer is sputtered onto the base element according to microcircuit fabrication techniques).
A sensor element of the invention can emit different types (generally EM waves are lumped by frequency ranges over the EM Frequency Spectrum) of measurable emissions when exposed to a time-varying interrogation magnetic field. The interrogation field may be generated continuously over time (such as over a selected time interval) or the interrogation field may be generated in the form of a pulse, after which the measurement of emission intensity is made. Depending upon the receiver, the emissions measured may be acoustic, electromagnetic, or optical in nature. Electromagnetic emissions are received by an EM pick-up coil. If acoustic emissions from a sensor element are targeted, an electroacoustic receiving device containing a transducer for operation over a range of frequencies from 1 KHz to 1 GHz may be used. Optical waves are received by an optical receiving device.
Associated with the apparatus disclosed hereby, the invention also covers a method for determining elasticity characteristics of a thin-film layer at least partially coating a surface of a base magnetostrictive element. In a first characterization of the method of the invention, steps include: applying a time-varying interrogation magnetic field to a sensor element comprising the base magnetostrictive element and thin-film layer, operatively arranged to vibrate in response to the interrogation magnetic field (box 102, FIG. 17); remotely measuring a plurality of values for magneto-elastic emission intensity of the sensor element to identify a magneto-elastic resonant frequency value therefor (box 104, FIG. 17); and using a value for density of the thin-film layer, a value for mass of the base magnetostrictive elements and and magneto-elastic resonant frequency value, determining at least one of the elasticity characteristics (box 108, FIG. 17).
In a second characterization of the method of the invention, once a time-varying interrogation magnetic field is applied to a sensor element comprising the base magnetostrictive element and thin-film layer of a fluent bio-substance (box 102, FIG. 17), a plurality of successive values for magneto-elastic emission intensity of the sensor element at a preselected magneto-elastic frequency are remotely measured (box 104, FIG. 17). Using the values for emission intensity measured over a selected response-time interval, an elasticity response profile for the bio-substance can be produced (box 109, FIG. 17. The elasticity response profile can comprise a coagulation reaction curve, or other bioactive reaction response curve, for the bio-substance. Other information relating to elasticity characteristics of the thin-film fluent bio-substance layer can be obtained according to the invention, including clotting/coagulation time, enzyme reaction time, pathogen growth, and so on (box 112, FIG. 17).